1. Field of the Invention
The present invention relates to an improved apparatus and method for detecting contrast agents in ultrasonic imaging and, in particular, apparatus and methods for use of quadrature demodulation in detecting contrast agents.
2. Background of the Invention
Ultrasonic transducers and imaging systems are used in many medical applications and, in particular, for the non-invasive acquisition of images of organs and conditions within a patient, typical examples being the ultrasound imaging of fetuses and the heart. Such systems commonly use a linear or phased array transducer having multiple transmitting and receiving elements to transmit and receive narrowly focused and xe2x80x9csteerablexe2x80x9d beams, or xe2x80x9clinesxe2x80x9d, of ultrasonic energy into and from the body. The received beams, or lines, are reflected from the body""s internal structures and contain amplitude or phase information, or both, that is used to generate images of the body""s internal structures.
A primary problem in ultrasonic imaging has been that many of the body""s internal structures have similar characteristics as regards the reflection of ultrasonic energy, so that it is difficult to obtain as clear and detailed images as is desired of many of the structures, such as the muscles of the heart.
This problem led to the development of alternative methods for imaging certain of the body""s structures, such as the blood vessels of the heart. One of the most common imaging techniques, for example, referred to as an angiogram, requires the injection of a radio-opaque dye into the vessels to image the blood vessels of the heart with x-rays. Such techniques, however, are invasive or are otherwise unsatisfactory. For example, the use of x-ray imaging carries the risk of potential injury from radiation and involves complex, expensive and hazardous equipment. Also, radio-opaque dyes are potentially toxic to at least some patients and are not broken down in the body but are flushed from the body by natural waste processes, often requiring hours to disappear from the body.
A more recent development has been ultrasonic imaging using contrast agents injected into the blood stream. Ultrasonic contrast agents are now commercially available and are essentially small bubbles of gas, such as air, formed by agitating a liquid or bubbling gas through a liquid, such as a saline solution or a solution containing a bubble forming compound, such as albumin. When insonicated, the bubbles resonate at their resonant frequency and at the second harmonic of their resonant frequency, thereby returning an enhanced signal at or around these frequencies and thereby providing an enhanced image of the liquid or tissue containing the contrast agent. It is also well known that the bubbles xe2x80x9cdisappearxe2x80x9d when insonicated at a high enough power level and the current theory is that the insonication ruptures the bubble""s shell, thereby allowing the gas to dissipate into the surrounding liquid or tissue.
The use of ultrasonic contrast agents is thereby advantageous in allowing enhanced imaging using ultrasonics rather than x-rays, thereby eliminating the radiation hazard and allowing the use of equipment that is significantly less expensive and hazardous to use. Also, the agents are non-toxic and dissolve relatively quickly into waste products, such as air and albumin, that are normally found in the body and that are themselves non-toxic. Further, the insonication of the agent in itself destroys the agent, so that the agent can effectively be xe2x80x9cerasedxe2x80x9d during or after the imaging process.
There are, however, a number of persistent problems in ultrasonic imaging using contrast agents, many of which concern the detection of contrast agents in the tissues of interest and the measurement of contrast agent concentrations in the tissues of interest.
For example, many ultrasonic imaging systems using contrast agents generate the desired image from two or more successive returned signals wherein the first returned signal is the sum of a component due to the bubbles being destroyed by the insonication and other components from other sources, such as the tissue, clutter and bubbles that were not destroyed by the insonication. The second returned signal includes components from the other sources, such as the tissue, clutter and bubbles that were not destroyed, but does not have a component from the bubbles being destroyed by the insonication that generated the first returned signal. As a consequence, an image primarily representing the contrast agent, that is, the bubbles being destroyed by the insonication, and thus an enhanced image of the tissues containing the contrast agent, can be generated by subtracting the components of the second returned signal from the components of the first returned signal.
This method may also be used to determine the concentration of contrast agent in the tissues of interest by determining the change in the returned signals between the first and second or later returned, and is thereby useful in other applications. For example, the change in concentration of contrast agent in the tissues of interest may be used to determine the rate of perfusion, that is, blood flow, in the tissues of interest. In a further extension of this method, the difference in rate of perfusion between, for example, a ischemia infarction and the heart muscle tissues may be used to detect the boundaries between the ischemia infarction and surrounding muscle tissue and thereby to generate enhanced images of the heart.
In another example, the ability to control the concentration of contrast agent in a region of interest, for example, by selectably destroying contrast agent through controlled insonication, is a significant advantage because too high a concentration of contrast agent results in saturation and non-linear, flat images due to interference between the bubbles. Also, and as a related problem, a too high a concentration of contrast agent in regions between the transducer and the region of interest will result in a shadowing effect wherein the near region image return will shadow, that is, hide or at least degrade the image in the region of interest.
All of these techniques, however, require the detection of contrast agents in the tissues of interest, or the measurement of contrast agent concentrations in the tissues of interest.
Broadly, the two primary methods for determining the components in returned signals or the difference in components between successive returned signals are, first, simply measuring the amplitude of the returned signals, and, second, measuring the complex vector components, that is, the phasor components, of the returned signals, for example, by quadrature demodulation of the returned signals into their amplitude and phase components. Of these two methods, quadrature demodulation would be generally preferred, for example, as providing more complete and detailed information regarding the returned signals and thus potentially providing superior images.
In quadrature demodulation, however, the returned signal at any particular spatial location in the tissues of interest is generally a complex number, or phasor. That is, the first returned signal is the vector sum of a phasor component due to the bubbles being destroyed by the insonication and other phasor components from other sources, such as the tissue, clutter and bubbles that were not destroyed by the insonication. The second returned signal, in turn, includes phasor components from the other sources, such as the tissue, clutter and bubbles that were not destroyed, but does not have a phasor component from the bubbles being destroyed by the insonication that generated the first returned signal.
The phasor components of the second returned signal, however, will generally differ to a greater or lessor degree from the corresponding phasor components of the first returned signal because of blood, tissue or transducer motion. This difference will generally primarily appear as a phase rotation, and will generally be a relatively small fraction of a cycle because of the relative short time between transmit pulses, and thus between returned signals.
In addition, however, the burst bubble phasor component of the first returned signal will be uncorrelated in both magnitude and phase with the phasor components from other sources, such as the tissue, clutter and bubbles that were not destroyed, and can cause the returned signal to be larger or smaller in magnitude or advanced or retarded in phase, or any combination thereof, compared to what the returned signal would be without the component from bursting bubbles. As such, and although the expected value of the magnitude should be greater with the bursting bubble component than without, the actual value of the magnitude of the returned signal could be larger, the same as, or smaller than without the component from bursting bubbles, depending upon the relative phases of the signal components. Still further, the magnitude of the return signal will vary randomly due to xe2x80x9cspecklexe2x80x9d and noise, although the system noise component may be negligible in the case of bubbles perfusing in dense tissues.
Any method for detecting one speckly signal in the presence of another uncorrelated speckly signal or detecting one variable magnitude signal by comparison to another variable magnitude signal by thresholding will therefore provide an uncertain result at the yes/no boundary in the decision process.
Because of these problems, many systems of the prior art use only the difference in magnitude between the signals, for example, detecting only the magnitude of the second harmonic of the returned signal as the second harmonic component is primarily due to the contrast agent. Certain of the systems of the prior art have even explicitly rejected the use of phase dependent information, stating that not using phase related information is an essential key to the detection of contrast agents because it allows the destruction of bubbles to be distinguished from echo change due to motion of the tissue or the transducer. The systems of the prior art have also been based on the principle that detection thresholds are not dependent upon any signal characteristic.
There are grounds to believe, however, as discussed in the following description of the invention, that the systems of the prior art using these approaches are incorrect in these assumptions and that they accordingly do not provide optimum results.
The present invention therefore provides a solution to these and other problems of the prior art by providing improved methods for the use of contrast agents.
The present invention is directed to an apparatus and a method for using quadrature demodulation to detect a contrast agent in an ultrasonic echographic system which receives ultrasonic return signals containing components due to tissues and possibly due to a contrast agent wherein each return signal represents an image along a single receiving line of a transducer. According to the present invention, a quadrature demodulation contrast agent detector includes an in phase/quadrature demodulator for determining the in phase and quadrature components of each return signal, wherein the in phase and quadrature components of each return signal are the resolved complex components, real and imaginary, of each return signal that are respectively in phase with and in quadrature phase with a reference signal, and a contrast agent detector for determining the complex difference between a first return signal and a second return signal and generating a complex difference value representing the complex difference.
The contrast agent detector of the present invention may be embodied in a number of implementations, one of which is a magnitude of difference detector for determining the magnitude of the complex difference of pairs of a first return signal and a second return signal wherein both the real and imaginary components of the return signals, which include both magnitude and phase information, are used to determine the magnitude of the complex difference between the first and second return signals.
The magnitude of difference contrast agent detector includes a complex difference calculator for determining the difference between the in phase and quadrature components of the first and second return signals and generating a complex difference value for each pair of first and second return signals wherein each complex difference value will have an in phase component and a quadrature component representing the complex difference between the real and imaginary components of the first and second return signals. A magnitude resolver is connected from the complex difference calculator for resolving the in phase and quadrature components of the complex difference value for each pair of first and second return signals and generating a difference magnitude value representing the magnitude of the complex difference between the real and imaginary components of each pair of first and second return signals. A threshold comparator then compares the value of the difference magnitude value of each pair of first and second return signals with a predetermined, selectable threshold value and generates an output representing a contrast agent component when a difference magnitude value exceeds the threshold value.
The magnitude of difference contrast agent detector may also include a memory for receiving and storing the in phase and quadrature components of the first return signal and providing the in phase and quadrature components of the first return signal to the complex difference calculator, and a bypass connected around the memory for providing the in phase and quadrature components of the second return signal to the complex difference calculator concurrently with the stored in phase and quadrature components of the first return signal.
The magnitude of difference contrast agent detector may also be implemented with a second magnitude resolver for receiving the in phase and quadrature components of the second return signal and determining a second magnitude value representing the magnitude of the second return signal, including both contributions from the tissue and from other causes and sources other than the contrast agent, and a multiplier for receiving the second magnitude value and multiplying the second magnitude value by a predetermined value to generate a threshold value representing a proportion of the signal magnitude from sources other than the contrast agent.
The magnitude of difference contrast agent detector may further be implemented with a second magnitude resolver for receiving the in phase and quadrature components of the second return signal and determining a second magnitude value representing the magnitude of the second return signal, including both contributions from the tissue and from other causes and sources other than the contrast agent, and a divider for receiving the difference magnitude value and the second magnitude value and dividing the value of the difference magnitude value by the value of the second magnitude value to generate the threshold value thereby scaling the difference magnitude value relative to a selectable fixed threshold value to provide a variable threshold value relative to the magnitude of the second return signal, including both contributions from the tissue and from other causes and sources other than the contrast agent.
It is known that the change in a background echo, that is, in everything except the bursting bubbles, is primarily a phase rotation. For this reason, and in yet a further alternate embodiment, the quadrature demodulation contrast agent detector may be implemented as an asymmetrical weighting detector for resolving the complex difference between first and second return signals into components in phase with and orthogonal to the second signal and weighting these two components differently for generating corresponding threshold values for the in phase and orthogonal components of the complex difference between the first and second return signals wherein a contrast agent is indicated when the weighted combination of the in phase or orthogonal components exceeds the corresponding threshold value.
The asymmetrical weighting contrast agent detector includes a complex difference calculator for determining the difference between the in phase and quadrature components of the first and second return signals and generating a complex difference value for each pair of first and second return signals wherein each complex difference value has a real component value which represents the difference between the real components of the first and second return signals and an imaginary component value which represents the difference between the imaginary components of the first and second return signals. A magnitude resolver is connected from the complex difference calculator for receiving the second return signal and generating a value representing the magnitude of the second return signal, and the detector further includes a first divider for receiving the complex difference value and dividing the real and imaginary component values by the value representing the magnitude of the second return signal and generating a scaled complex difference signal representing the complex difference between the first and second return signals, and a second divider for receiving the second return signal and the value representing the magnitude of the second return signal and dividing the second return signal by the value representing the magnitude of the second return signal for generating a unit magnitude signal representing the real and imaginary components of the second return signal and in phase with the second return signal. A conjugate multiplier then receives the outputs of the first and second dividers and multiplies the scaled complex difference signal by the conjugate of the unit magnitude signal to generate a scaled complex difference signal rotated in the complex plane and having a real component representing the scaled complex difference in phase with the second return signal and an imaginary component orthogonal to the second return signal. An asymmetric weighted combiner then receives the rotated scaled complex difference signal, weights the real and imaginary components of the rotated scaled complex difference signal with corresponding coefficients, and combines the weighted real and imaginary components to generate a combined magnitude value. A threshold comparator then compares the combined magnitude value with a predetermined, selectable threshold value and generates an output representing a contrast agent component when a difference magnitude value exceeds the threshold value.
The asymmetrical weighting detector may also include a memory for receiving and storing the in phase and quadrature components of the first return signal and providing the in phase and quadrature components of the first return signal to the complex difference calculator, and a bypass connected around the memory for providing the in phase and quadrature components of the second return signal to the complex difference calculator, to the magnitude resolver and to the first divider concurrently with the stored in phase and quadrature components of the first return signal.
In another alternate embodiment, the asymmetric weighted combiner may weight the real and imaginary components of the rotated scaled complex difference signal by separately squaring and adding the real and imaginary components with different weighting coefficients so that the combined magnitude value that is compared to the threshold defines an elliptical threshold in the complex plane.
In yet another alternate embodiment, the asymmetric weighted combiner may weight the absolute value of the real and imaginary components of the rotated scaled complex difference signal by adding the real and imaginary components with corresponding weighting coefficients so that the combined magnitude value that is compared to the threshold defines a rhomboidal threshold in the complex plane.
In another alternate embodiment, the asymmetric weighted combiner weights the real and imaginary components of the rotated scaled complex difference signal by separately weighting the real and imaginary components with corresponding coefficients and comparing the greater of the weighted real and imaginary components with the threshold so that the combined magnitude value that is compared to the threshold defines a rectangular threshold in the complex plane.
In yet another embodiment, the contrast agent detector may be implemented as an extrapolation detector for receiving three successive return signals along each receiving line wherein the second return signal and a third return signal are used to extrapolate what the first return signal would have been without the contrast agent component and to generate a decision threshold that is compared to the complex difference between the actual first return signal and the extrapolated first return signal.
According to the present invention, the extrapolation contrast agent detector includes a complex summer for receiving the first, second and third return signals and performing a complex phasor summation of the first, second and third return signals to generate a complex sum that represents the difference between the actual first return signal and an extrapolated first return signal generated from the second and third return signals and without a contribution from a contrast agent, a first magnitude resolver for receiving the complex and generating a value representing the magnitude of the complex sum, and a second magnitude resolver for receiving the second return signal and generating a value representing the magnitude of the second return signal. A multiplier receives the value representing the magnitude of the second return signal and multiplies the value representing the magnitude of the second return signal by a coefficient to generate a threshold value, and a threshold comparator for receives the threshold value and the complex sum representing the difference between the actual first return signal and the extrapolated first return signal and generates an output representing whether the magnitude of the complex sum exceeds the threshold value.
In one embodiment of the extrapolation contrast agent detector, the complex summer generates a complex sum of the first, second and third return signals wherein the first and third return signals are summed with multipliers of +1 and the second return signal is summed with a xe2x88x922 multiplier. Further in this embodiment, the extrapolation detector may further include a first memory and a second memory, each for receiving and storing the first, second and third return signals, wherein the first memory provides the first return signal to the complex summer and the second memory provides the second return signal to the complex summer and to the first magnitude resolver, and a bypass for providing the third return signal to the complex summer.
In an alternate embodiment, the extrapolation contrast agent detector may include a first complex difference calculator for generating a first complex difference between the first and second return signals and a second complex difference calculator for generating a second complex difference representing the complex difference between two successive first complex differences, wherein the second complex difference thereby represents the complex difference between the actual first return signal and an extrapolated first return signal generated from the second and third return signals and not including a contrast agent component. This embodiment further includes a magnitude resolver for receiving the second return signal and generating a value representing the magnitude of the second return signal, a multiplier for receiving the value representing the magnitude of the second return signal and multiplying the value representing the magnitude of the second return signal by a coefficient to generate a threshold value, and a threshold comparator for receiving the threshold value and the complex sum representing the difference between the actual first return signal and the extrapolated first return signal and generating an output representing whether the complex sum exceeds the threshold value.
Finally, in this embodiment the extrapolation contrast agent detector may further include a first memory for storing the first return signal, the second return signal and the third return signal and providing the first return signal to the first complex difference calculator, a first bypass for providing the second return signal to the first difference calculator in conjunction with the first return signal from the first memory and the second return signal to the magnitude resolver, a second memory for storing the first complex difference between the first and second return signals and the second complex difference representing the complex difference between the second and third return signals, and a second bypass for providing the second complex difference between the second return signal and the third return signal to the second complex difference calculator in conjunction with the first complex difference between the first return signal and the second return signal from the second memory.
In yet other embodiments of the extrapolation contrast agent detector, the quadrature demodulation contrast agent detector is expanded to deal with more than three return signals by means of a complex summer for receiving the first return signal and n subsequent successive return signals and performing a complex phasor summation of the first return signal and the n subsequent successive return signals to generate a complex sum that represents the difference between the actual first return signal and an extrapolated first return signal generated from the n subsequent successive return signals and without a contribution from a contrast agent. A first magnitude resolver then receives the complex sum and generates a value representing the magnitude of the complex sum while a second magnitude resolver for receives the n subsequent successive return signals and generates a value representing the magnitude of the n subsequent successive return signals. A multiplier receives the value representing the magnitude of the n subsequent successive return signals and multiplies the value representing the magnitude of the n subsequent successive return signals by a coefficient to generate a threshold value, and a threshold comparator receives the threshold value and the complex sum representing the difference between the actual first return signal and the extrapolated first return signal and generates an output representing whether the complex sum exceeds the threshold value.
Further according to this embodiment of the extrapolation contrast agent detector, the first and n subsequent successive return signals in a given direction are interleaved with a first and n subsequent successive return signals in at least one other given direction and an extrapolated first return signal is generated for each given direction.
Other features, objects and advantages of the present invention will be understood by those of ordinary skill in the art after reading the following descriptions of a present implementation of the present invention, and after examining the drawings, wherein: